Michael T Heneka1,2,3, Anne Fink1,4, Gabriele Doblhammer1,4,5,6. 1. German Center for Neurodegenerative Diseases, Bonn, Germany. 2. Clinical Neurosciences, Department of Neurology, University of Bonn, Bonn, Germany. 3. Department of Medicine, University of Massachusetts Medical School, Worcester, MA. 4. Rostock Center for the Study of Demographic Change, Rostock, Germany. 5. Institute for Sociology and Demography, University of Rostock, Rostock, Germany. 6. Max Planck Institute for Demographic Research, Rostock, Germany.
Abstract
OBJECTIVE: Peroxisome proliferator activated receptor γ-activating drugs show various salutary effects in preclinical models of neurodegenerative disease. The decade-long clinical usage of these drugs as antidiabetics now allows for evaluation of patient-oriented data sources. METHODS: Using observational data from 2004-2010, we analyzed the association of pioglitazone and incidence of dementia in a prospective cohort study of 145,928 subjects aged ≥60 years who, at baseline, were free of dementia and insulin-dependent diabetes mellitus. We distinguished between nondiabetics, diabetics without pioglitazone, diabetics with prescriptions of <8 calendar quarters of pioglitazone, and diabetics with ≥8 quarters. Cox proportional hazard models explored the relative risk (RR) of dementia incidence dependent on pioglitazone use adjusted for sex, age, use of rosiglitazone or metformin, and cardiovascular comorbidities. RESULTS: Long-term use of pioglitazone was associated with a lower dementia incidence. Relative to nondiabetics, the cumulative long-term use of pioglitazone reduced the dementia risk by 47% (RR = 0.53, p = 0.029). If diabetes patients used pioglitazone <8 quarters, the dementia risk was comparable to those of nondiabetics (RR = 1.16, p = 0.317), and diabetes patients without a pioglitazone treatment had a 23% increase in dementia risk (RR = 1.23, p < 0.001). We did not find evidence for age effects, nor for selection into pioglitazone treatment due to obesity. INTERPRETATION: These findings indicate that pioglitazone treatment is associated with a reduced dementia risk in initially non-insulin-dependent diabetes mellitus patients. Prospective clinical trials are needed to evaluate a possible neuroprotective effect in these patients in an ageing population.
OBJECTIVE: Peroxisome proliferator activated receptor γ-activating drugs show various salutary effects in preclinical models of neurodegenerative disease. The decade-long clinical usage of these drugs as antidiabetics now allows for evaluation of patient-oriented data sources. METHODS: Using observational data from 2004-2010, we analyzed the association of pioglitazone and incidence of dementia in a prospective cohort study of 145,928 subjects aged ≥60 years who, at baseline, were free of dementia and insulin-dependent diabetes mellitus. We distinguished between nondiabetics, diabetics without pioglitazone, diabetics with prescriptions of <8 calendar quarters of pioglitazone, and diabetics with ≥8 quarters. Cox proportional hazard models explored the relative risk (RR) of dementia incidence dependent on pioglitazone use adjusted for sex, age, use of rosiglitazone or metformin, and cardiovascular comorbidities. RESULTS: Long-term use of pioglitazone was associated with a lower dementia incidence. Relative to nondiabetics, the cumulative long-term use of pioglitazone reduced the dementia risk by 47% (RR = 0.53, p = 0.029). If diabetespatients used pioglitazone <8 quarters, the dementia risk was comparable to those of nondiabetics (RR = 1.16, p = 0.317), and diabetespatients without a pioglitazone treatment had a 23% increase in dementia risk (RR = 1.23, p < 0.001). We did not find evidence for age effects, nor for selection into pioglitazone treatment due to obesity. INTERPRETATION: These findings indicate that pioglitazone treatment is associated with a reduced dementia risk in initially non-insulin-dependent diabetes mellituspatients. Prospective clinical trials are needed to evaluate a possible neuroprotective effect in these patients in an ageing population.